CE/CME

Pediatric T2DM: A Growing Threat to US Health

Clinician Reviews. 2015 March;25(3):34-42

References

1. Fryar CD, Carroll MD, Ogden CL. Prevalence of obesity among children and adolescents: United States, trends 1963-1965 through 2009-2010. CDC. National Center for Health Statistics, Health E-Stat, September 2012.
2. Cote AT, Harris KC, Panagiotopoulos C, et al. Childhood obesity and cardiovascular dysfunction. J Am Coll Cardiol. 2013;62(15):1309-1319.
3. Dabelea D, Bell RA, D’Agostino Jr RB, et al; the SEARCH for Diabetes in Youth Writing Group. Incidence of diabetes in youth in the United States. JAMA. 2007;297(24):2716-2724.
4. Copeland KC, Silverstein J, Moore KR, et al. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Pediatrics. 2013;131(2):364-382.
5. American Diabetes Association. Children and adolescents. Sec. 11. In: Standards of Medical Care in Diabetes—2015. Diabetes Care. 2015;38(suppl 1):S70-S76.
6. Constantino MI, Molyneaux L, Limacher-Gisler F, et al. Long-term complications and mortality in young-onset diabetes. Diabetes Care. 2013;36:3863-3869.
7. CDC. National Diabetes Statistics Report, 2014: Estimates of Diabetes and its Burden in the United States. www.cdc.gov/diabetes/pubs/statsre port14/national-diabetes-report-web.pdf. Accessed February 17, 2015.
8. Pettitt DJ, Talton J, Dabelea D, et al; for the SEARCH for Diabetes in Youth Study Group. Prevalence of diabetes in US youth in 2009: the SEARCH for Diabetes in Youth Study. Diabetes Care. 2014;37:402-408.
9. Imperatore G, Boyle JP, Thompson TJ, et al; for the SEARCH for Diabetes in Youth Study Group. Projections of type 1 and type 2 diabetes burden in the U.S. population aged < 20 years through 2050. Diabetes Care. 2012;35:2515-2520.
10. Dabelea D, Mayer-Davis EJ, Saydah S, et al; for the SEARCH for Diabetes in Youth Study Group. Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA. 2014;311(17):1778-1786.
11. Lifshitz F (ed). Pediatric Endocrinology. Vol 1. 5th ed. New York; Informa Healthcare: 2006.
12. DeFronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes. Diabetes. 2009;58:773-795.
13. Flint A, Arslanian B. Treatment of type 2 diabetes in youth. Diabetes Care. 2011;34(suppl 2):S177-S183.
14. American Diabetes Association. Type 2 diabetes in children and adolescents: consensus statement. Diabetes Care. 2000;23(3):381-389.
15. American Diabetes Association. Classification and diagnosis of diabetes. Sec. 2. In: Standards of Medical Care in Diabetes—2015. Diabetes Care. 2015;38(suppl 1):S8-S16.
16. FDA. FDA allows marketing of first ZnT8Ab autoantibody test to help diagnose type 1 diabetes. Press release. August 20, 2014.
17. Klingensmith GJ, Pyle L, Arslanian S, et al; the TODAY Study Group. The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype-results from the TODAY study. Diabetes Care. 2010;33(9):1-6.
18. Silverstein J, Klingensmith G, Copeland K, et al. American Diabetes Association. Care of children and adolescents with type 1 diabetes. Diabetes Care. 2005;28(1):186-212.
19. Academy of Nutrition and Dietetics. Pediatric weight management guideline (2007). www.andeal.org/topic.cfm?cat=2721. Accessed February 17, 2015.
20. Glucophage [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2009.
21. American Association of Clinical Endocrinologists/American College of Endocrinology. Consensus statement by the AACE/ACE insulin pump management task force. Endocr Prac. 2014;20(5):463-489.
22. American Diabetes Association. Management of diabetes in pregnancy. Sec. 12. In: Standards of Medical Care in Diabetes—2015. Diabetes Care. 2015;38(suppl 1):S77-S79.
23. TODAY Study Group. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med. 2012;366(24):2247-2256.
24. FDA. Drug safety communication. FDA requires removal of some prescribing and dispensing restrictions for rosiglitazone-containing diabetes medicines. www.fda.gov/downloads/Drugs/DrugSafety/UCM381108.pdf. Accessed February 17, 2015.
25. National Heart Lung and Blood Institute. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report. Pediatrics. 2011;128(suppl 5):S213-S256.
26. Peters A, Laffel L; American Diabetes Association Transitions Working Group. Diabetes care for emerging adults: recommendations for transition from pediatric to adult diabetes care systems. Diabetes Care. 2011;34(11):2477-2485.

First-line medication: Metformin
If treatment goals are not met with lifestyle changes, treatment with metformin should be initiated.^4,14 Metformin is currently the only FDA-approved oral agent for the treatment of T2DM in children, although it is not recommended for use in those younger than 10.²⁰ Metformin improves glycemic control by increasing insulin action, decreasing gluconeogenesis, and decreasing glucagon secretion.¹¹Metformin may also regulate ovulation in patients with PCOS, increasing the patient’s fertility. Adolescent female patients being treated with metformin should avoid pregnancy because its use is not recommended during pregnancy.^14,20

Because metformin carries a black box warning for a rare but life-threatening complication—lactic acidosis—the clinician should confirm normal renal function before treatment initiation. Renal function should be monitored regularly (at least annually during metformin treatment and more often if impaired renal function is anticipated) and metformin discontinued if impaired renal function is present. Risk is also reduced by use of the lowest effective dose.²⁰

To minimize common gastrointestinal adverse effects, metformin should be taken with meals. Treatment should be initiated at a dose of 500 mg/d,⁴ with slow titration upward by 500 mg/wk, as needed and tolerated, until an effective maintenance dose is reached. Maintenance doses may range from 500 mg/d to 2,000 mg/d (taken in divided doses).²⁰

Metformin use can result in moderate decreases in BG and A1C levels. In addition, because metformin does not stimulate insulin secretion, the risk for hypoglycemia is minimal.²⁰ The clinician may consider monitoring vitamin B₁₂ levels, particularly in a population already at risk for peripheral neuropathy, because metformin increases risk for vitamin B₁₂ deficiency.²⁰

As T2DM progresses, metformin alone may be insufficient for maintenance of glycemic control.

Insulin therapy
Treatment with insulin therapy, rather than metformin, should be initiated in pediatric diabetes patients if the diagnosis of T2DM is not confirmed or for those patients who present with ketosis or ketoacidosis.⁴

Insulin therapy should also be initiated for patients with confirmed T2DM if random tests for plasma BG levels are 250 mg/dL or higher or A1C levels are more than 9.0%.⁴ Reflecting the lack of consensus on pediatric T2DM treatment, the ADA recommends insulin therapy when the A1C level is greater than 8.5%.¹³ Insulin may be used in conjunction with metformin, which may decrease the insulin dosage that would otherwise be needed due to metformin’s ability to increase insulin sensitivity.⁴

Insulin regimens
Selection of the appropriate insulin regimen depends on clinician judgment, patient and family comfort level, and lifestyle considerations. Initial barriers for the patient and family may include resistance to injecting medication, difficulty understanding instructions for insulin therapy, and fear of weight gain or hypoglycemia. Close monitoring for significant day-to-day fluctuations in the pediatric patient’s activity levels or diet is essential in order to adjust insulin dosage as needed and prevent hyperglycemia or hypoglycemia.

The types of insulin therapy include
Basal. Basal insulin at bedtime with insulin detemir or glargine is a straightforward method of insulin delivery, with lower risk for hypoglycemia. The ADA recommends initial dosing at 0.3 to 0.4 U/kg/d for the pediatric population, titrating slowly until FBG is at goal without hypoglycemia.¹³

Basal-bolus. If postprandial BG or A1C levels remain elevated, basal insulin provides the groundwork for intensification to a physiologic basal-bolus regimen with addition of insulin lispro, aspart, or glulisine. Bolus insulin therapy can be in the form of a fixed mealtime dose or as an insulin-to-carbohydrate ratio, as caretaker comfort and patient lifestyle permit.¹¹

In patients who are not able to adhere to a basal-bolus regimen due to multiple daily injections, consider conservative treatment with twice-daily insulin NPH as basal therapy, with or without short-acting insulin at breakfast and dinner.¹¹

An alternative for adults that is occasionally used in youth (although not yet FDA-approved for this use) is twice-daily premixed insulin aspart 70/30 or lispro 75/25. While this regimen can improve compliance, it does not permit mealtime adjustments in insulin dosing and requires a snack between meals to prevent hypoglycemia.¹¹

Families will sometimes choose insulin pump therapy for a pediatric patient with T2DM.¹¹ For these patients, use of the insulin pump requires a motivated family committed to BG monitoring at least four times a day and in possession of a good working knowledge of basic diabetes management.²¹

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